Human Papillomavirus-Related CarcinomaPhase 1NCT04580446
HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer
A Phase 1 study testing Hypofractionated intensity modulated radiotherapy in people with Human Papillomavirus-Related Carcinoma and Oropharyngeal Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
This is a single arm Phase I study of de-intensified hypofractionated radiation therapy for favorable human papilloma virus-associated oropharynx cancer. It will evaluate the tolerability of a de-intensified hypofractionated radiation therapy regimen completed in 3 weeks (with equivalent biologically effective dose to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Papillomavirus-Related Carcinoma, Oropharyngeal Cancer
- What is being tested?
- Hypofractionated intensity modulated radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Dec 2020to 20 Dec 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically-proven diagnosis of T1-3 (up to 6 cm), N0-2 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx (except T1-2N0 as noted in the exclusion criteria)
- ≤10 pack-year smoking history and not actively smoking
- Age ≥18 years
- ECOG performance status 0-2 or Karnofsky Performance Status 50-100
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.
- Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- Distant metastasis
- T1-2N0 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx (candidates for definitive RT alone or surgery alone)
- Inability to receive concurrent weekly cisplatin due to comorbid conditions
- Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and well-differentiated thyroid cancer. For prostate cancer, patient should not be receiving active treatment. For thyroid cancer, thyroid surgery may occur before or after radiation treatment, provided all other eligibility criteria are met.
- Prior invasive malignancy with an expected disease-free interval of less than 3 years
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields
Show all 11Show fewer
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- History of severe immunosuppression, including HIV, organ or autologous or allogeneic stem cell transplant, or active immunosuppressive medication at the time of enrollment
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: HYHOPE: Phase I Study of De-intensified Hypofractionated Radiation Therapy for Human Papilloma Virus-associated Oropharynx Cancer
This is a single arm Phase I study of de-intensified hypofractionated radiation therapy for favorable human papilloma virus-associated oropharynx cancer. It will evaluate the tolerability of a de-intensified hypofractionated radiation therapy regimen completed in 3 weeks (with equivalent biologically effective dose to 60 Gy in 30 fractions) with concurrent weekly cisplatin.
Read the detailed description
Standard of care radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC) involves conventional fractionation delivered over a course of 7 weeks. Although hypofractionated RT (HFRT) delivering higher dose of RT each day over a shorter overall treatment time has been studied and adopted as standard of care in many disease sites including breast and prostate cancers, data on HFRT in HNSCC is limited.
There is a strong radiobiological rationale for HFRT for HNSCC to decrease the overall treatment time and thus the effects of accelerated repopulation in this disease entity. In addition, if similar outcomes can be achieved with a reduced number of fractions, cost effectiveness of care can be improved while minimizing the disruption to the patient's personal and professional lives. A substantial decrease in treatment time may improve compliance and financial toxicity associated with the patient's oncologic treatment.
The global COVID-19 pandemic is highlighting the health risk to society at large of having no viable alternative to a 7 week daily RT course for HNSCC, especially in the setting of compromised immune systems associated with concurrent chemotherapy frequently used in this patient population. Thus, the study of HFRT for HNSCC is both timely and potentially paradigm changing for practices across the United States.
The incidence of human papilloma virus (HPV)-associated oropharynx cancer is increasing in the United States, now accounting for 70-80% of all oropharynx cancers. It has a favorable prognosis vs. non-HPV-associated cancers and studies are ongoing to determine the best strategy to de-intensified therapy while maintaining good oncologic outcomes.
The purpose of this single-arm Phase I study is to assess the tolerability and signal for efficacy of de-intensified HFRT for favorable HPV-associated oropharynx cancer. De-intensification will be achieved in two ways. First, the equivalent biologically effective dose (BED) of HFRT used on trial will be 60 Gy of conventionally fractionationated RT (vs. the current standard of care of 70 Gy). Second, the elective nodal volume irradiated will be limited to involved nodal levels and one immediately adjacent level (vs. the current standard of care of entire bilateral neck nodal regions). Patients will complete RT in 15 fractions (3 weeks) with concurrent weekly cisplatin on dose level 0. If a 3-week regimen is not well-tolerated, a 20 fraction regimen will be used on dose level -1.
- Being tested
- Hypofractionated intensity modulated radiotherapy
- Keywords
- Radiation Dose Hypofractionation
- Medical subject headings
- Oropharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypofractionated intensity modulated radiotherapyRadiation
Hypofractionated intensity modulated radiotherapy with concurrent chemotherapy (weekly cisplatin)
| Study group | Role | What they receive |
|---|---|---|
| Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2) | Experimental | Level 0: 46.5 Gy in 15 fractions, 5 fractions/week
Level -1: 52 Gy in 20 fractions, 5 fractions/week Receives: Radiation: Hypofractionated intensity modulated radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximally Tolerated Dose/Fractionation of Hypofractionated Radiation Therapy
The number of participants experiencing dose-limiting toxicities (DLTs) will be used to determine the maximally tolerated dose (MTD) or optimal fractionation of hypofractionated radiation therapy.
Level 0: 46.5 Gy in 15 fractions Level -1: 52 Gy in 20 fractions
Measured: 3 months
Secondary outcomes (9)
Clinician-reported Acute Toxicities
Toxicities as measured by CTCAE v5.0
Measured: 0-3 months
Clinician-reported Late Toxicities
As measured by CTCAE v5.0
Measured: 3-12 months
Percentage of Participants With Locoregional Control
Locoregional control defined as freedom from locoregional recurrence. Locoregional recurrence defined as biopsy-proven viable cancer originating from the primary tumor site (i.e. oropharynx) or a lymph node basin above the clavicles.
Measured: 12 months
Percentage of Participants With Progression Free Survival
Progression-free survival defined as time from start of treatment to time of progression or death.
Measured: 1-12 months
Percentage of Participants With Overall Survival
Overall survival defined as time from start of treatment o time of death.
Measured: 24 months
Swallowing-related Patient-reported Quality of Life
Change from baseline in swallowing-related quality of life, as measured by the MD Anderson Dysphagia Inventory (MDADI) total score, assessed at specified time points (baseline,1, 3, 6, and 12 months) during and after treatment. Higher scores indicate better function, 0-100. Analyses were descriptive, and a paired t test was used to compare questionnaire results over time with P < .05 considered statistically significant. MDADI composite score difference of 10 was deemed clinically meaningful.
Measured: 1-12 months
Head and Neck Patient-reported Quality of Life
Change from baseline in head and neck patient-reported outcomes quality of life, as measured by the University of Washington Quality of Life questionnaire (UW-QOL), assessed at specified time points (baseline,1, 3, 6, and 12 months) during and after treatment. Higher scores on UW-QOL subscales indicate better quality of life, 0 being worst and 100 being the best outcome. A paired t test was used to compare questionnaire results over time with P < .05 considered statistically significant. UW-QOL was divided into 2 subscales of physical and social-emotional function with change of 0.5 x standard deviation (SD) and 0.8 x SD considered moderate and large effect, respectively.
Scale title: Patient-reported quality of life at baseline and after treatment (0-100) Physical UW-QOL minimum: 45.83 Physical UW-QOL maximum: 100 Social-Emotional UW-QOL minimum: 17.5 Social-Emotional UW-QOL maximum: 100
Measured: 1-12 months
General Patient-reported Quality of Life
EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life. Index score: 0-1, higher scores mean better quality of life. Visual Analog scale: 0-100, higher scores mean better quality of life.
Measured: 1-12 months
Feeding Tube Dependence
Dependence on tube feeds defined as any participant with daily use of ≥2 nutritional supplements per day via the feeding tube at the time of evaluation.
Measured: 1-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start3 Dec 2020
- Primary completion20 Dec 2024
- Study completion20 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Human Papillomavirus-Related CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Rolling 6 dose finding cohort followed by dose expansion cohort
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Gateway for Cancer Research
- Responsible party
- Principal investigator, Dominic Moon, University of Texas Southwestern Medical Center
- Investigators
- Dominic Moon, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04580446
- Sponsor's protocol ID
- STU-2020-1079
- Status last verified
- Nov 2025
- First submitted
- 1 Oct 2020
- Last updated
- 15 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HYHOPE: Phase I Study of De-intensified Hypofractionated Radiation Therapy for Human Papilloma Virus-associated Oropharynx Cancer
- ClinicalTrials.gov ID
- NCT04580446
- Acronym / sponsor ID
- STU-2020-1079
- Keywords
- Radiation Dose Hypofractionation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Gateway for Cancer Research
- Study start
- 3 Dec 2020 (actual)
- Primary completion
- 20 Dec 2024 (actual)
- Study completion
- 20 Dec 2024 (actual)
- First posted
- 8 Oct 2020 (actual)
- Results
- Posted 15 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm Phase I study of de-intensified hypofractionated radiation therapy for favorable human papilloma virus-associated oropharynx cancer. It will evaluate the tolerability of a de-intensified hypofractionated radiation therapy regimen completed in 3 weeks (with equivalent biologically effective dose to 60 Gy in 30 fractions) with concurrent weekly cisplatin.
Detailed description
Standard of care radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC) involves conventional fractionation delivered over a course of 7 weeks. Although hypofractionated RT (HFRT) delivering higher dose of RT each day over a shorter overall treatment time has been studied and adopted as standard of care in many disease sites including breast and prostate cancers, data on HFRT in HNSCC is limited.
There is a strong radiobiological rationale for HFRT for HNSCC to decrease the overall treatment time and thus the effects of accelerated repopulation in this disease entity. In addition, if similar outcomes can be achieved with a reduced number of fractions, cost effectiveness of care can be improved while minimizing the disruption to the patient's personal and professional lives. A substantial decrease in treatment time may improve compliance and financial toxicity associated with the patient's oncologic treatment.
The global COVID-19 pandemic is highlighting the health risk to society at large of having no viable alternative to a 7 week daily RT course for HNSCC, especially in the setting of compromised immune systems associated with concurrent chemotherapy frequently used in this patient population. Thus, the study of HFRT for HNSCC is both timely and potentially paradigm changing for practices across the United States.
The incidence of human papilloma virus (HPV)-associated oropharynx cancer is increasing in the United States, now accounting for 70-80% of all oropharynx cancers. It has a favorable prognosis vs. non-HPV-associated cancers and studies are ongoing to determine the best strategy to de-intensified therapy while maintaining good oncologic outcomes.
The purpose of this single-arm Phase I study is to assess the tolerability and signal for efficacy of de-intensified HFRT for favorable HPV-associated oropharynx cancer. De-intensification will be achieved in two ways. First, the equivalent biologically effective dose (BED) of HFRT used on trial will be 60 Gy of conventionally fractionationated RT (vs. the current standard of care of 70 Gy). Second, the elective nodal volume irradiated will be limited to involved nodal levels and one immediately adjacent level (vs. the current standard of care of entire bilateral neck nodal regions). Patients will complete RT in 15 fractions (3 weeks) with concurrent weekly cisplatin on dose level 0. If a 3-week regimen is not well-tolerated, a 20 fraction regimen will be used on dose level -1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Rolling 6 dose finding cohort followed by dose expansion cohort
| Arm | Type | Receives |
|---|---|---|
| Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2) | Experimental | Radiation: Hypofractionated intensity modulated radiotherapyLevel 0: 46.5 Gy in 15 fractions, 5 fractions/week Level -1: 52 Gy in 20 fractions, 5 fractions/week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Pathologically-proven diagnosis of T1-3 (up to 6 cm), N0-2 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx (except T1-2N0 as noted in the exclusion criteria)
- ≤10 pack-year smoking history and not actively smoking
- Age ≥18 years
- ECOG performance status 0-2 or Karnofsky Performance Status 50-100
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Key exclusion criteria (11 listed)
- Distant metastasis
- T1-2N0 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx (candidates for definitive RT alone or surgery alone)
- Inability to receive concurrent weekly cisplatin due to comorbid conditions
- Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and well-differentiated thyroid cancer. For prostate cancer, patient should not be receiving active treatment. For thyroid cancer, thyroid surgery may occur before or after radiation treatment, provided all other eligibility criteria are met.
- Prior invasive malignancy with an expected disease-free interval of less than 3 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypofractionated intensity modulated radiotherapyHypofractionated intensity modulated radiotherapy with concurrent chemotherapy (weekly cisplatin) | Radiation | Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2) |
Primary outcome
Maximally Tolerated Dose/Fractionation of Hypofractionated Radiation Therapy
Time frame: 3 months
The number of participants experiencing dose-limiting toxicities (DLTs) will be used to determine the maximally tolerated dose (MTD) or optimal fractionation of hypofractionated radiation therapy. Level 0: 46.5 Gy in 15 fractions Level -1: 52 Gy in 20 fractions
9 secondary outcomes
Clinician-reported Acute Toxicities
Time frame: 0-3 months
Clinician-reported Late Toxicities
Time frame: 3-12 months
Percentage of Participants With Locoregional Control
Time frame: 12 months
Percentage of Participants With Progression Free Survival
Time frame: 1-12 months
Percentage of Participants With Overall Survival
Time frame: 24 months
Swallowing-related Patient-reported Quality of Life
Time frame: 1-12 months
Head and Neck Patient-reported Quality of Life
Time frame: 1-12 months
General Patient-reported Quality of Life
Time frame: 1-12 months
Feeding Tube Dependence
Time frame: 1-12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominic Moon, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hypofractionated intensity modulated radiotherapy in people with Human Papillomavirus-Related Carcinoma and Oropharyngeal Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximally Tolerated Dose/Fractionation of Hypofractionated Radiation Therapy (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.